The long-term goals of this Program Project are to elucidate the mechanisms by which HSV-1 establishes, maintains and reactivates from neuronal latency. The Specific Aims of each of these projects address distinct but related aspects of the long-term goals. Although much of the work in all three projects will be conducted at the molecular level and many studies will initially be conducted in non-neuronal cells, it is essential that the relevance of findings made in these studies to HSV-1 latency and disease be examined in mammalian neurons and in animal models. The mouse core was developed specifically for this purpose. It will provide a source of latently infected TG and TG cell cultures and their uninfected counterparts for investigators in all three Projects. As the best-studied, least expensive and most reliable animal model for the study of HSV-1 latency extant in the field today, the availability of the mouse model of latency and reactivation and the mouse core are essential components of this Program Project. Because (i) 60-90% of individuals world-wide are infected with HSV-1 (ii) 50% of these individuals experience recurrent disease and (iii) HSV-1 infection can be life-threatening to the subset of infected persons who are immunocompromised, the mouse model of latency and the mouse core provide an essential bridge between results obtained in this Program Project at the bench and the development of effective antiviral strategies for use in treating HSV-1 infected patients.